Pharmaceutical composition for overcoming resistance in antimicrobial-resistant strains

Composition for Restoring Susceptibility to Carbapenem-Resistant Klebsiella pneumoniae Using Deletion Gene Supplementation

This technology provides a composition that restores antimicrobial susceptibility in carbapenem-resistant Klebsiella pneumoniae by supplementing the deleted KPHS_46730 or KPHS_33600 genes or their proteins, as well as a screening method for identifying resistant bacteria and overcoming agents using the expression of these genes as markers.

Antimicrobials are widely used not only in pharmaceuticals but also as preservatives in food and cosmetics; however, their use has been increasingly restricted due to the rise of bacteria resistant to chemical antimicrobials. In particular, Klebsiella pneumoniae, which shows resistance to carbapenems—often called the "last-resort" antibiotics—lacks effective treatment options, and the inability to rapidly detect resistance has led to the misuse and overuse of antimicrobials.

This technology increases the expression of gene products missing in resistant bacteria to levels found in susceptible strains, ensuring sufficient bactericidal effects at the same antimicrobial concentration, and predicts the presence of resistant bacteria in patients by measuring gene expression. Applicable to adjuvant therapies for multidrug-resistant infections, combination antibiotic therapies, diagnostic kits, and drug screening, it extends the lifespan of existing carbapenem antibiotics and enables personalized antimicrobial prescriptions.

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Key Features:

• Composition for enhancing susceptibility to carbapenem-resistant Klebsiella pneumoniae, comprising at least one of the KPHS_46730 gene, the KPHS_33600 gene, or their encoded proteins as an active ingredient
• Composition for antimicrobial treatment of resistant Klebsiella pneumoniae, comprising a carbapenem-based antimicrobial and the KPHS_46730 gene or its encoded protein as active ingredients
• Step of screening for resistant strains by measuring the expression level of the KPHS_46730 or KPHS_33600 gene or protein in a biological sample containing Klebsiella pneumoniae
• Step of treating a resistant bacterial sample with a candidate substance and selecting it as an agent to overcome resistance if the expression of the corresponding gene increases to the level of a susceptible strain

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This invention was developed with support from the Multi-Ministry Genome Project for the cultivation of post-genome new industries, funded by the Ministry of Agriculture, Food and Rural Affairs.

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